Embryonal rhabdomyosarcoma

by Jason Wasserman MD PhD FRCPC
March 13, 2023

What is embryonal rhabdomyosarcoma?​

Embryonal rhabdomyosarcoma is a type of cancer made up of immature muscle cells. These tumours typically start in the head, neck, or genitourinary tract. Most embryonal rhabdomyosarcomas occur in children although they can also occur in adults.

What genetic syndromes are associated with embryonal rhabdomyosarcoma?

People with Costello syndrome, neurofibromatosis type 1, Noonan syndrome, Beckwith–Wiedemann syndrome, DICER1 syndrome, and Li–Fraumeni syndrome have an increased risk of developing embryonal rhabdomyosarcoma.

How is embryonal rhabdomyosarcoma diagnosed?

The first diagnosis of embryonal rhabdomyosarcoma is usually made after a small sample of the tumour is removed in a procedure called a biopsy. The biopsy tissue is then sent to a pathologist who examines it under a microscope. After a pathologist makes a diagnosis of embryonal rhabdomyosarcoma, patients are often treated first with chemotherapy and/or radiation therapy followed by surgery. The tumour is then removed completely as a resection specimen and sent to pathology for examination.

What does embryonal rhabdomyosarcoma look like under the microscope?

When examined under the microscope, the tumour is made up of immature muscle cells called rhabdomyoblasts. The nucleus of the cell (the part that holds the genetic material of the cell) is typically small, round and hyperchromatic (dark blue). The nucleus of the cell may be eccentric (pushed to the side of the cell) and a small amount of pink cytoplasm (the material inside the body of the cell) may be seen beside the nucleus.

What other tests may be performed to confirm the diagnosis?

Immunohistochemistry

Immunohistochemistry is a special test that allows pathologists to look for specific types of proteins inside cells. Pathologists use the results of this test to determine the cell’s function and where in the body the cell came from. When immunohistochemistry is performed on embryonal rhabdomyosarcoma, the tumour cells are typically positive for muscle markers such as desmin, myogenin, and MyoD1.

Molecular tests

Molecular tests such as fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) may be performed to look for specific genetic changes. The primary reason for performing these types of tests on embryonal rhabdomyosarcoma is to help rule out other types of rhabdomyosarcoma that can look very similar when examined under the microscope. For example, alveolar rhabdomyosarcoma contains a genetic change involving the FOXO1 gene but this change is not seen in embryonal rhabdomyosarcoma.

What grade is embryonal rhabdomyosarcoma?

At present, pathologists do not provide a grade for embryonal rhabdomyosarcoma.

Why is the size of the tumour important for embryonal rhabdomyosarcoma?

Tumour size is important because tumours less than 5 cm are less likely to spread to other parts of the body and are associated with a better prognosis. Tumour size is also used to determine the pathologic tumour stage (pT).

What does tumour extension mean?

Most embryonal rhabdomyosarcomas start inside of a muscle, but the tumour can grow into other organs or tissues outside of the muscle. This is called tumour extension. Your pathologist will examine samples of the surrounding organs and tissues under the microscope to look for tumour cells. Any surrounding organs or tissue that contain tumour cells will be described in your report.

What does perineural invasion mean and why is it important?

Perineural invasion is a term pathologists use to describe cancer cells attached to or inside a nerve. A similar term, intraneural invasion, is used to describe cancer cells inside a nerve. Nerves are like long wires made up of groups of cells called neurons. Nerves are found all over the body and they are responsible for sending information (such as temperature, pressure, and pain) between your body and your brain. Perineural invasion is important because the cancer cells can use the nerve to spread into surrounding organs and tissues. This increases the risk that the tumour will regrow after surgery.

What does lymphovascular invasion mean and why is it important?

Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs. Embryonal rhabdomyosarcoma very rarely shows lymphovascular invasion.

What is a margin and why are margins important?

In pathology, a margin is the edge of a tissue that is cut when removing a tumour from the body. The margins described in a pathology report are very important because they tell you if the entire tumour was removed or if some of the tumour was left behind. The margin status will determine what (if any) additional treatment you may require.

Most pathology reports only describe margins after a surgical procedure called an excision or resection has been performed for the purpose of removing the entire tumour. For this reason, margins are not usually described after a procedure called a biopsy is performed for the purpose of removing only part of the tumour. The number of margins described in a pathology report depends on the types of tissues removed and the location of the tumour. The size of the margin (the amount of normal tissue between the tumour and the cut edge) depends on the type of tumour being removed and the location of the tumour.

Pathologists carefully examine the margins to look for tumour cells at the cut edge of the tissue. If tumour cells are seen at the cut edge of the tissue, the margin will be described as positive. If no tumour cells are seen at the cut edge of the tissue, a margin will be described as negative. Even if all of the margins are negative, some pathology reports will also provide a measurement of the closest tumour cells to the cut edge of the tissue.

A positive (or very close) margin is important because it means that tumour cells may have been left behind in your body when the tumour was surgically removed. For this reason, patients who have a positive margin may be offered another surgery to remove the rest of the tumour or radiation therapy to the area of the body with the positive margin. The decision to offer additional treatment and the type of treatment options offered will depend on a variety of factors including the type of tumour removed and the area of the body involved.

What does treatment effect mean?

If you have been diagnosed with embryonal rhabdomyosarcoma on a biopsy, you may be offered chemotherapy and/or radiation therapy before the operation to remove your tumour. If you have received either of these treatments before your surgery, your pathologist will examine all the tissue sent to pathology to see how much of the tumour is still alive (viable).

There are different systems used to describe the treatment effects for rhabdomyosarcoma. Most commonly, your pathologist will describe the percentage of tumour that is dead. Pathologists use the word necrosis to describe dead (non-viable) tumour.

A tumour showing 90% or more therapy response (meaning 90% of the tumour is dead and 10% or less of the tumour is still alive) is considered a good response to therapy and is associated with a better prognosis.

What is the the pathologic stage (pTNM) for embryonal rhabdomyosarcoma?

​Tumours in adults are given a pathologic stage based on the TNM staging system, an internationally recognized system originally created by the American Joint Committee on Cancer. The TNM system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means more advanced disease and a worse prognosis. Tumours that start in the head and neck are not staged using this system.

Tumours in children are given a pathologic stage based on a modified TNM staging system (the Intergroup Rhabdomyosarcoma Study Group grouping system). This system uses information about the location of the tumour and the type of surgery performed in order to determine the final pathologic stage.  All of this information is then combined to determine the risk of cancer coming back in the future.

Tumour stage (pT) for embryonal rhabdomyosarcoma in adults

The method for determining the tumour stage depends on the area of the body involved. For example, a 5-centimetre tumour that starts in the chest will be given a different tumour stage than a tumour that starts deep in the back of the abdomen (the retroperitoneum). However, in most body sites, the tumour stage includes the tumour size and whether the tumour has grown into surrounding body parts.

Chest, back, or stomach and the arms or legs (trunk and extremities)

• T1 – The tumour is no greater than 5 centimetres in size.
• T2 – The tumour is between 5 and 10 centimetres in size.
• T3 – The tumour is between 10 and 15 centimetres in size.
• T4 – The tumour is greater than 15 centimetres in size.

Abdomen and organs inside the chest (thoracic visceral organs)

• T1 – The tumour is only seen in one organ.
• T2 – The tumour has grown into the connective tissue that surrounds the organ from which is started.
• T3 – The tumour has grown into at least one other organ.
• T4 – Multiple tumours are found.

Retroperitoneum (the space at the very back of the abdominal cavity)

• T1 – The tumour is no greater than 5 centimetres in size.
• T2 – The tumour is between 5 and 10 centimetres in size.
• T3 – The tumour is between 10 and 15 centimetres in size.
• T4 – The tumour is greater than 15 centimetres in size.

Nodal stage (pN) for embryonal rhabdomyosarcoma in adults

Embryonal rhabdomyosarcoma is given a nodal stage of 0 or 1 based on the presence of tumour cells in a lymph node. If no tumour cells are seen in any of the lymph nodes examined, the nodal stage is N0. If tumour cells are seen in any of the lymph nodes examined, the nodal stage becomes N1.

Metastatic stage (pM) for embryonal rhabdomyosarcoma in adults

Embryonal rhabdomyosarcoma is given a metastatic stage of 0 or 1 based on the presence of tumour cells at a distant site in the body (for example the lungs). The metastatic stage can only be determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.